The newborn of the woman with diabetes mellitus (classes A, B, or C) is at an increased risk of succumbing to idiopathic respiratory distress syndrome (RDS) of the newborn; a disease resulting from inadequate production of lung surfactant. During fetal lung maturation in the pregnancy complicated by diabetes mellitus (Classes A, B, or C), the first appearance of surfactant, and the developmental change from a surfactant rich in phosphatidylinositol (PI) to mature surfactant enriched in phosphatidylglycerol (PG), are both delayed events. In the diabetic person there is an imbalance in inositol homeostasis and there is evidence that this is important in certain diseases arising as sequelae to diabetes mellitus. Since it is known that the relative availability of inositol affects the metabolism of several lipids, it is possible that if an imbalance in inositol homeostasis in the pregnant woman with diabetes mellitus were to give rise to altered inositol metabolism in her fetus, fetal lung maturation may be affected adversely. We will determine if abnormal metabolism of inositol by the fetus interferes with the biosynthesis of the principal component of surfactant, viz., dipalmitoyl phosphatidylcholine, and/or delays the developmental change from a surfactant rich in PI to one rich in PG. The glucose-intolerant pregnant rabbit will be employed as a model of the human pregnancy complicated by diabetes mellitus. The source(s) of inositol for the fetus and the effect of maternal glucose-intolerance on inositol homeostasis in the fetus will be investigated. Inositol levels in the developing rabbit fetus will be manipulated experimentally and the mechanism of any effect on surfactant production and composition will be investigated. In particular, the possible competition between inositol, choline, and glycerol-3-phosphate for common precursors in the biosynthesis of PI, PC, and PG will be studied. Inositol levels in human amniotic fluid will be measured in an attempt to determine if there is altered inositol availability in the fetus during the pregnancy complicated by diabetes mellitus. We will assess the merit of measurements of inositol in human amniotic fluid for the identification of those fetuses of diabetic gravida who are destined to suffer from RDS.